Dimeric compounds and their use as anti-viral agents

Abstract

The invention relates to compounds of general formula (I); in which R is an amino or guanidino group; R 2 is acetyl or trifluoroacetyl; and n is an integer from 10 to 18 or a pharmaceutically acceptable derivative thereof, methods for their preparation, pharmaceutical formulations containing them or their use in the prevention or treatment of a viral infection

1. A compound of general formula (I): 
       
         
           
           
               
               
           
         
       
       in which
 R is an amino or guanidino group; 
 R 2  is acetyl or trifluoroacetyl; and 
 n is an integer from 10 to 14, 
 
       or a pharmaceutically acceptable salt, ether, ester or salt of such ester thereof. 
     
     
       2. A compound according to  claim 1 , in which R is a guanidino group. 
     
     
       3. A compound according to  claim 1 , in which R 2  is an acetyl group. 
     
     
       4. A compound according to  claim 1 , in which n is 12 to 14. 
     
     
       5. A compound according to  claim 1 , which contains a pharmaceutically acceptable salt, ether, ester or salt of such ester at one or more of the carboxyl groups, hydroxyl groups, amino groups or guanidine groups. 
     
     
       6. A compound according to  claim 1 , in which said compound is an alkyl ester, an aryl ester or an acetyl ester. 
     
     
       7. A method for the preparation of the compound of formula (I) according to  claim 1 , which comprises the step of deprotecting a compound of formula (II) 
       
         
           
           
               
               
           
         
         in which n is as defined in  claim 1 , P 1  is a carboxylic acid protecting group and P 2  is an amine protecting group. 
       
     
     
       8. A method for the preparation of the compound of formula (I) according to  claim 1 , which comprises the steps of;
 (a) reacting a compound of formula (III) 
 
       
         
           
           
               
               
           
         
          in which P 1  is a carboxylic acid protecting group and P 2  is an amine protecting group, with a compound of formula (IV):
   OCN(CH 2 ) n NCO  (IV) 
 
          in which n is as defined in  claim 1 , 
       
       to form the compound of formula (II) 
       
         
           
           
               
               
           
         
          in which n is as defined in  claim 1 , P 1  is a carboxylic acid protecting group and P 2  is an amine protecting group; and 
         (b) deprotecting the compound of formula (II). 
       
     
     
       9. A method for the preparation of the compound of formula (I) according to  claim 1 , which comprises the steps of:
 (a) protectinig a compound of formula (V) 
 
       
         
           
           
               
               
           
         
          in which P 1  is a carboxylic acid protecting group and P 2  is an amine protecting group to form the compound of formula (III) 
       
       
         
           
           
               
               
           
         
          in which P 1  is a carboxylic acid protecting group and P 2  is an amine protecting group; 
         (b) reacting the compound of formula (III) with the compound of formula (IV)
   OCN(CH 2 ) n NCO  (IV) 
 
          in which n is as defined in  claim 1   
       
       to form the compound of formula (II) 
       
         
           
           
               
               
           
         
          in which n is as defined in  claim 1 , P 1  is a carboxylic acid protecting group and P 2  is an amine protecting group.; and 
         (c) deprotecting the compound of formula (II). 
       
     
     
       10. A pharmaceutical formulation comprising a therapeutically effective amount of a compound of formula (I) as defined in  claim 1  or a pharmaceutically acceptable salt, ether, ester or salt of such ester thereof, together with one or more pharmaceutically acceptable carriers. 
     
     
       11. A pharmaceutical formulation according to  claim 10 , which further comprises one or more anti-viral agents used to treat respiratory infections. 
     
     
       12. A pharmaceutical formulation according to  claim 11 , in which the agent is zanamivir, oseltamivir, amantadine, rimantadine, and/or ribavirin. 
     
     
       13. An inhaler which comprises a compound according to  claim 1 . 
     
     
       14. An inhaler according to  claim 13  which is adapted for oral administration as a free-flow powder. 
     
     
       15. An inhaler according to  claim 13  which is a metered dose aerosol inhaler. 
     
     
       16. A method for treatment of an orthomyxovirus or paramyxovirus infection, comprising the step of administration to a subject in need thereof of an effective amount of a compound of formula (I) as defined in  claim 1 . 
     
     
       17. A method according to  claim 16  in which the orthomyxovirus or paramyxovirus infection is an influenza A or B infection, parainfluenza, mumps or Newcastle disease. 
     
     
       18. A method according to  claim 16  in which the administration is to the respiratory tract by inhalation, insufflation or intranasally or a combination thereof. 
     
     
       19. A method for the detection of an orthomyxovirus or paramyxovirus infection which comprises the step of contacting the compound of formula (I) as defined in  claim 1  with a sample suspected of containing the virus. 
     
     
       20. A method according to  claim 16 , further comprising the step of administering an effective amount of one or more anti-viral agents used to treat respiratory infections.